On the failure of modern species concepts

The modern age of species concepts began in 1942, when Ernst Mayr gave concept names to several different approaches to species identification. A long list of species concepts then followed, as well as a complex literature on their merits, motivations and uses. Some of these complexities arose as a consequence of the semantic shift that Mayr introduced, in which procedures for identifying species were elevated to concepts. Much of the debate in recent decades over concepts, and over pluralism versus monism, can be seen as an unnecessary consequence of treating species identification criteria as if they were more fundamental concepts. Recently, biologists have begun to recognize both the shortcomings of a lexicon of multiple species concepts and a common evolutionary idea that underlies them.     

Generation and characterization of a humanized bradykinin B1 receptor mouse

Antagonists of the B1 bradykinin receptor (B1R), encoded by the BDKRB1 gene, offer the promise of novel therapeutic agents for inflammatory and neuropathic pain. However, the in vivo characterization of the pharmacodynamics of B1R antagonists is hindered by the low level of B1R expression in healthy tissue and the profound species selectivity exhibited by many compounds for the B1R. To circumvent these issues we generated two genetically engineered rodent models. The first is a transgenic rat over-expressing the human B1R under the control of the neuronal-specific enolase promoter; we previously reported the utility of this model in assessing human B1R receptor occupancy in the central nervous system of the rat. The second model, reported here, utilized gene-targeting by homologous recombination to replace the genomic coding sequence for the endogenous mouse B1R with that of the human B1R. The mRNA expression profile of the humanized Bdkrb1 (hBkdrb1) allele is similar to that of the mouse Bdkrb1 (mBkdrb1) in the wild-type animal. Furthermore, in vitro assays indicate that tissues isolated from the humanized mouse possess pharmacological properties characteristic of the human B1R. Therefore, we have generated a humanized B1R mouse model that is suitable for testing the efficacy of human B1R-selective compounds.     

Relationship between alpha synuclein phosphorylation, proteasomal inhibition and cell death: relevance to Parkinson's disease pathogenesis

Alpha synuclein can be phosphorylated at serine129 (P-S129), and the presence of highly phosphorylated α-synuclein in Lewy bodies suggests changes to its phosphorylation status has an important pathological role. We demonstrate that the kinase(s) responsible for α-synuclein S129 phosphorylation is constitutively active in SH-SY5Y cells and involves casein kinase 2 activity. Increased oxidative stress or proteasomal inhibition caused significant elevation of P-S129 α-synuclein levels. Under these conditions, similar increases in P-S129 α-synuclein were found in both sodium dodecyl sulphate lysates and Triton extracts indicating the phosphorylated protein was soluble and did not lead to aggregation. The rate of S129 phosphorylation was increased in response to proteasomal inhibition indicating a higher activity of the relevant kinase. Cells expressing the phosphorylation mimic, S129D α-synuclein increased cell death and enhanced sensitivity to epoxomycin exposure. Proteasomal inhibition markedly decreased S129D α-synuclein turnover suggesting proteasomal inhibition leads to the accumulation of P-S129 α-synuclein through an increase in the kinase activity and a decrease in protein turnover resulting in increased cell death. We conclude that S129 phosphorylation is toxic to dopaminergic cells and both the levels of S129 phosphorylated protein and its toxicity are increased with proteasomal inhibition emphasising the interdependence of these pathways in Parkinson's disease pathogenesis.     

Anti‐fibrotic effect of chorionic plate‐derived mesenchymal stem cells isolated from human placenta in a rat model of CCl4‐injured liver: Potential application to the treatment of hepatic diseases

Translational studies have explored the therapeutic effects of stem cells, raising hopes for the treatment of numerous diseases. Here, we evaluated the therapeutic effect of chorionic plate‐derived mesenchymal stem cells (CP‐MSCs) isolated from human placenta and transplanted into rats with carbon tetrachloride (CCl₄)‐injured livers. CP‐MSCs were analyzed for hepatocyte‐specific gene expression, indocyanine green (ICG) uptake, glycogen storage, and urea production following hepatogenic differentiation. PKH26‐labeled CP‐MSCs were directly transplanted into the livers of rats that had been exposed to CCl₄ (1.6 g/kg, twice per week for 9 weeks). Blood and liver tissue were analyzed at 1, 2, and 3 weeks post‐transplantation. The expression of type I collagen (Col I) and matrix metalloproteinases (MMPs) was analyzed in rat T‐HSC/Cl‐6 hepatic stellate cells co‐cultured with CP‐MSCs following exposure to TGF‐β. The expression levels of α‐smooth muscle actin (α‐SMA) and Col I were lower in transplanted (TP) rats than in non‐transplanted (Non‐TP) animals (P < 0.05), whereas the expression levels of albumin and MMP‐9 were increased. TP rats exhibited significantly higher uptake/excretion of ICG than non‐TP rats (P < 0.005). In addition, collagen synthesis in T‐HSC/Cl‐6 cells exposed to TGF‐β was decreased by co‐culture with CP‐MSCs, which triggered the activation of MMP‐2 and MMP‐9. These results contribute to our understanding of the potential pathophysiological roles of CP‐MSCs, including anti‐fibrotic effects in liver disease, and provide a foundation for the development of new cell therapy‐based strategies for the treatment of difficult‐to‐treat liver diseases. J. Cell. Biochem. 111: 1453–1463, 2010. © 2010 Wiley‐Liss, Inc.     

Historical trends in frog populations in New Zealand based on public perceptions

Surveys were distributed to New Zealand land users in 1998 and 2008 to acquire information about New Zealand frogs with the aim of compiling and mapping their distribution and inferred population trends without costly and time-consuming field surveys. The overall frog population trend was reported as declining, with possible causes reported as an increase in agriculture, an increase in the distribution of predatory fish and disease. The resultant maps could be used for four main purposes: 1) to identify regions where Litoria populations are known to occur, which can be eliminated when considering suitable regions for translocation of Leiopelma; 2) to identify growing or stable populations of Litoria species, which may assist future disease surveys, population monitoring and to identify sources of genetic material that may serve as an Ark for declining Australian populations; 3) to highlight populations that are in decline to enable effective targeting of detailed disease studies; and 4) to approximate the stability of amphibian populations in the absence of more accurate, but costly, scientific monitoring.